Overview of the First NRG Oncology–National Cancer Institute Workshop on Dosimetry of Systemic Radiopharmaceutical Therapy

Abstract

In 2018, the National Cancer Institute (NCI) and the NRG Oncology partnered for the first time to host a joint Workshop on Systemic Radiopharmaceutical Therapy (RPT) to specifically address issues and strategies of dosimetry for future clinical trials. The workshop focused on (1) current dosimetric approaches for clinical trials, (2) strategies under development that would provide optimal dose reporting, and (3) future desired/optimized approaches for the new and novel emerging radionuclides and carriers in development. In this proceedings, we review the main approaches that are applied clinically to calculate the absorbed dose: These include absorbed doses calculated over a variety of spatial scales including "whole body", organ, sub-organ, and voxel, the latter three all achievable within the Medical Internal Radiation Dose (MIRD) schema (S-value) can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This proceeding will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biological effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We also briefly discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation-when merited by evidence collected during earlyphase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.

Nonclinical Study and Applicability of the Absorbed Dose Conversion Method With a Single Biodistribution Measurement for Targeted Alpha-Nuclide Therapy

“…At present, one of issues in systemic radiopharmaceutical therapy or TAT is optimizing imaging time points [2]. The previous work of Madsen et al [3] revealed a single-time to estimate the total integrated activity and absorbed dose to within 10% accuracy.…”

“…Tb1 and Tb2 are the corresponding HL times (sec) for fast and slow biological clearances, respectively. Or, in the case of adrenals and tumor tissue, the following one-compartment equation was used: ( ) = 0 (− (2) ) { (−…”

Combining External Beam Radiation and Radionuclide Therapies: Rationale, Radiobiology, Results and Roadblocks

“…This has been compounded by there being no recommendation, until recently, to tailor the amount of administered radioactivity in MRT treatments to individual patients. This has been partly remedied through the implementation of international directives recommending that MRT be individually planned, and its delivery verified, usually through single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging [8,9]. In this review, MRT is defined as the use of systemically or regionally administered radiopharmaceuticals that incorporate b-electron-, a-particle-or Auger electron-emitting radionuclides for cancer therapy.…”

National Cancer Institute support for targeted alpha-emitter therapy

“…These workshops built upon prior workshops and symposia focused on RPT and TAT led by individual efforts by or collaborations between Department of Energy (DOE), various NIH institutes, National Academy of Sciences, and/or SNMMI [8][9][10]. More recently, the NCI-SNMMI workshops provided a forum for stakeholders representing different disciplines in academia, industry, and the government agencies to discuss not only the advances, but also the challenges of RPT and how to address them [11,12].…”

“…Robust evidence in support of this concept is necessary, which requires multidisciplinary collaboration. The NCI brought together experts in the elds of nuclear medicine, radiation oncology, and medical physics for a workshop in 2018 to address issues and strategies of dosimetry for future clinical trials [11]. This meeting resulted in several publications [15][16][17] and creation of the NCI IROC Focus Group to provide support for RPT dosimetry methodology and expertise for principal investigators of NCI-funded RPT clinical trials.…”